Specific Aim 1: Develop a method for recording the focal EOG in response to a centrally presented light stimulus. A total of 20 healthy volunteers over the course of 1-3 study visits have participated in the study. Initial experiments to induce a dark trough before generating the light peak were shown to be highly variable. We shifted towards elimination of the dark trough in favor of generating a baseline dark amplitude during a long dark adaptation period of 40 minutes. For the light peak, we tested various stimulus sized and found that a 20o central stimulus was insufficient to generate a response from the target area, but a 40o central stimulus could produce the target response. Therefore, our current method is dark adaptation for 25 minutes, recording in the dark (to establish the baseline amplitude) for 20 minutes, then presentation of the light stimulus for 15 minutes. This method produces a recording lasting 35 minutes, which has been well-tolerated by all subjects. In order to test the response to centrally presented 40o light stimuli, volunteers were presented various central stimuli ranging from 10 to 150 cd/m2 in intensity. While 5/9 (56%) of eyes showed a light rise to 10 cd/m2, all 36 eyes tested showed light rises in response to intensities 40 cd/m2. Light peak:baseline averaged 1.370.19. Therefore, 40 cd/m2 appears to be the minimum 40 stimulus necessary and sufficient to generate a light rise. In order to test the variation in response to scattered light from central stimuli, various background intensities ranging from 0.4 cd/m2 to 1.1 cd/m2 were presented to volunteers. At the lowest background tested, participants had no or minimal light rise. The results above indicate that our method can measure an EOG light rise using a centrally presented 40 deg stimulus. The method for recording focal EOG requires that the background light be turned off for 10 seconds every minute. This is a departure from the standard focal EOG where the background remains on during the test. To determine whether these two methods produce different results, full-field EOGs were recorded from two healthy volunteers under identical conditions except for the two background conditions. The light rise portion of the intermittent background was within 10% of the continuously on-background indicating no meaningful difference between the background presentations. Specific Aim 2: Testing in healthy volunteers to determine intra- and inter-session variability. As noted for Aim 1, we have established the optimal stimulus parameters that produce a focal EOG in healthy volunteers. In 14 healthy volunteers, the Light peak:baseline ratio averaged 1.370.19. We have not yet attempted to measure variability in the focal EOG response. Specific Aim 3: Examine the focal EOG in participants with macular disease. We are currently enrolling maculopathy patients who meet specific criteria (central geographic atrophy, foveal preservation and a normal/near normal scotopic ERG) to test our hypothesis that a focal EOG is generated from the macula only with no scattered light component. Our initial results whilst promising were not sufficient to confirm that the focal EOG was truly a local response. In several participants, the focal EOG was absent and full-field EOG present as predicted. However, in the remaining Stargardt patients, there was a focal EOG of variable amplitude. We speculate that the size of atrophy was not a sufficiently large portion of the focal EOG stimulus size (40 deg) in some participants to sufficiently reduce the light rise response. We have expanded our recruitment to other participants with rare conditions affecting the macular, including one patient with variants in the melanogenesis associated transcription factor (MITF). We have recorded from two patients with large uveal colobomas. No focal EOG was recordable in either participant as predicted suggesting the focal EOG may be useful to examine participants with local defects in the retina/RPE complex. These results confirmed the utility of the technique to other conditions for whom it is unknown whether retina/RPE function is altered (e.g. MITF) or whether the extent of the malformation is sufficient to affect the focal EOG response (e.g. Uveal coloboma).